Your browser doesn't support javascript.
loading
17ß-estradiol inhibits spreading of metastatic cells from granulosa cell tumors through a non-genomic mechanism involving GPER1.
François, Charlotte M; Wargnier, Richard; Petit, Florence; Goulvent, Thibaut; Rimokh, Ruth; Treilleux, Isabelle; Ray-Coquard, Isabelle; Zazzu, Valeria; Cohen-Tannoudji, Joëlle; Guigon, Céline J.
Afiliação
  • François CM; INSERM U1133, Physiologie de l'Axe Gonadotrope, F-75013 Paris, France, Université Paris Diderot, Sorbonne Paris Cité, Biologie Fonctionnelle et Adaptative, F-75013 Paris, France, CNRS UMR 8251, Biologie Fonctionnelle et Adaptative, F-75013 Paris, France.
  • Wargnier R; INSERM U1133, Physiologie de l'Axe Gonadotrope, F-75013 Paris, France, Université Paris Diderot, Sorbonne Paris Cité, Biologie Fonctionnelle et Adaptative, F-75013 Paris, France, CNRS UMR 8251, Biologie Fonctionnelle et Adaptative, F-75013 Paris, France.
  • Petit F; INSERM U1133, Physiologie de l'Axe Gonadotrope, F-75013 Paris, France, Université Paris Diderot, Sorbonne Paris Cité, Biologie Fonctionnelle et Adaptative, F-75013 Paris, France, CNRS UMR 8251, Biologie Fonctionnelle et Adaptative, F-75013 Paris, France.
  • Goulvent T; U1052 INSERM, UMR CNRS 5286, Université de Lyon, Centre de Recherche en Cancérologie de Lyon, Centre Léon Bérard, Lyon F-69000, France, Institut Roche de Recherche et Médecine Translationnelle, 92650 Boulogne Billancourt, France.
  • Rimokh R; U1052 INSERM, UMR CNRS 5286, Université de Lyon, Centre de Recherche en Cancérologie de Lyon, Centre Léon Bérard, Lyon F-69000, France.
  • Treilleux I; Department of Pathology, Centre Léon Bérard, Lyon F-69000, France.
  • Ray-Coquard I; Department of Medical Oncology, Centre Léon Bérard, Université de Lyon, Lyon F-69000 and GINECO Group, Paris, France and.
  • Zazzu V; Institute of Genetics and Biophysics "A. Buzzati-Traverso"-CNR, I-80131 Naples, Italy.
  • Cohen-Tannoudji J; INSERM U1133, Physiologie de l'Axe Gonadotrope, F-75013 Paris, France, Université Paris Diderot, Sorbonne Paris Cité, Biologie Fonctionnelle et Adaptative, F-75013 Paris, France, CNRS UMR 8251, Biologie Fonctionnelle et Adaptative, F-75013 Paris, France.
  • Guigon CJ; INSERM U1133, Physiologie de l'Axe Gonadotrope, F-75013 Paris, France, Université Paris Diderot, Sorbonne Paris Cité, Biologie Fonctionnelle et Adaptative, F-75013 Paris, France, CNRS UMR 8251, Biologie Fonctionnelle et Adaptative, F-75013 Paris, France, celine.guigon@univ-paris-diderot.fr.
Carcinogenesis ; 36(5): 564-73, 2015 May.
Article em En | MEDLINE | ID: mdl-25823895
ABSTRACT
Granulosa cell tumor (GCT) is a rare and severe form of sex-cord stromal ovarian tumor that is characterized by its long natural history and tendency to recur years after surgical ablation. Because there is no efficient curative treatment beyond surgery, ~20% of patients die of the consequences of their tumor. However, very little is known of the molecular etiology of this pathology. About 70% of GCT patients present with elevated circulating estradiol (E2). Because this hormone is known to increase tumor growth and progression in a number of cancers, we investigated the possible role of E2 in GCTs. Cell-based studies with human GCT metastases and primary tumor-derived cells, ie KGN and COV434 cells, respectively, aimed at evaluating E2 effect on cell growth, migration and invasion. Importantly, we found that E2 did not affect GCT cell growth, but that it significantly decreased the migration and matrix invasion of metastatic GCT cells. Noteworthy, our molecular studies revealed that this effect was accompanied by the inhibition through non-genomic mechanisms of extracellular signal-regulated kinase 1/2 (ERK1/2), which is constitutively activated in GCTs. By using pharmacological and RNA silencing approaches, we found that E2 action was mediated by G protein-coupled estrogen receptor 1 (GPER1) signaling pathway. Analyses of GPER1 expression on tissue microarrays from human GCTs confirmed its expression in ~90% of GCTs. Overall, our study reveals that E2 would act via non-classical pathways to prevent metastasis spreading in GCTs and also reveals GPER1 as a possible target in this disease.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Receptores de Estrogênio / Movimento Celular / Receptores Acoplados a Proteínas G / Estradiol / Estrogênios / Tumor de Células da Granulosa / Recidiva Local de Neoplasia Tipo de estudo: Prognostic_studies Limite: Adult / Aged / Female / Humans / Middle aged Idioma: En Revista: Carcinogenesis Ano de publicação: 2015 Tipo de documento: Article País de afiliação: França

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Receptores de Estrogênio / Movimento Celular / Receptores Acoplados a Proteínas G / Estradiol / Estrogênios / Tumor de Células da Granulosa / Recidiva Local de Neoplasia Tipo de estudo: Prognostic_studies Limite: Adult / Aged / Female / Humans / Middle aged Idioma: En Revista: Carcinogenesis Ano de publicação: 2015 Tipo de documento: Article País de afiliação: França